The objective of this proposal is to provide powerful insight into the computational and neurobiological processes underlying learning during Pavlovian conditioning, and to elucidate the origin of differences between individuals in their response to a conditioned stimulus (CS), namely sign-trackers (ST) attracted by the CS and goal-trackers (GT) directly attracted by the reward. One of the project's partners recently proposed a computational model which accounts for a large set of studies examining ST/GT behaviors. More importantly, this model has led to a series of new experimental predictions which, if tested experimentally, could help further validate or refute the computational mechanisms that underlie everyday learning. Here we propose a unique series of model-driven experiments to precisely test those predictions on both the computational and neurobiological levels using rigorous behavioral protocols and state-of-the art optogenetic and pharmacogenetic methods. This will enable us to assess and refine the proposed computational theory, and thus to provide a detailed description of the mechanisms underlying inter-individual differences during learning. Intellectual Merit (provided by applicant): Understanding how the brain integrates predictive information is a fundamental issue and has major implications at both theoretical and applied levels. In both ecological and artificial situations, these processes enable animals, humans and even robots to flexibly adapt their performances according to changes in the environment. Particularly poorly understood here are the mechanisms underlying inter-individual differences in learning, which may explain why some individuals fail in learning in particular situations while others succeed. Understanding these individual differences can help us better characterize why some individuals are more prone to drug addiction and craving in front of a CS associated to a drug-taking context, and has implications about individualized treatment. The research herein draws on complementary expertise from Biology, Psychology, Medicine, Applied Mathematics and Engineering in order to elucidate the combination of computational processes and behavioral traits that underlie these differences. To this end, we will systematically manipulate parameters that the model identifies as crucial and evaluate the dynamics and role of dopaminergic error signaling. Our work involves a unique combination of correlative and selective interventional approaches that directly test the fundamental assumptions of the model. Our results will thus provide definitive evidence regarding the competition of model-free and model-based processes in conditioning. The computational model that is at the heart of this proposal may thus represent a major step in the approach of individual differences. Broader Impact (provided by applicant): The broader impacts of this proposal will occur through the integration of the proposed research with teaching and training as follows. 1) Outreach. The PI will broaden the participation of underrepresented groups through research opportunities provided to high school students and underrepresented undergraduates through an ongoing partnership with Eleanor Roosevelt High School. The latter program will consist of a 3-week scientific boot camp during the summer for 1-2 students followed by a year of research in the PI's lab 2) Professional development. This project will train one postdoc, three graduate students, at least three undergraduates, and several high school students in collaborative research. Tiered peer mentoring will allow training of new personnel by more senior lab members, all carried out under the guidance of the PI. 3) Teaching. The boot camp, developed by the PI, will provide students with a foundation in scientific methods and will use evidence-based approaches to introduce them to how scientists investigate research questions using techniques performed in the PI's lab. The French co-PIs will on their side continue their development of introductions to science classes for high-school students and courses at various university levels. 4) Dissemination of research findings. All trainees will present their research t lab meetings, journal clubs, and conferences and will participate in manuscript preparation in order to share results with the scientific community. All publications generated by the project wil be made open-access (via PI's faculty pages and HAL in France).